Brookes N
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.
J Neurochem. 1988 Apr;50(4):1117-22. doi: 10.1111/j.1471-4159.1988.tb10581.x.
Inhibition of glutamate transport is a potential indirect cause of excitotoxic damage by glutamate in the CNS. The mercuric ion, the form in which metallic mercury vapor is believed to exert its neurotoxic action, is a known inhibitor of amino acid transport. This study examines the specificity with which HgCl2 inhibits glutamate transport in mouse cerebral astrocytes by means of comparative measurements of 2-deoxyglucose uptake. Uptake of 2-deoxyglucose is an index of glucose utilization that reflects the function of Na+,K+-ATPase and hexokinase, and is sensitive to Na+ entry. The kinetic parameters, ionic dependence, and substrate specificity of glutamate transport in these astrocyte cultures were consistent with the commonly occurring system designated X-AG. Acute exposure to 0.5 microM HgCl2 inhibited by 50% the initial rate of glutamate transport but did not affect 2-deoxyglucose uptake. Glutamate transport was not detectably inhibited by Al2+, Pb2+, Co2+, Sr2+, Cd2+, or Zn2+ (10 microM as chlorides). The inhibitory action of 0.5 microM HgCl2 on glutamate transport was rapidly reversible. The action of 1-2 microM HgCl2 was progressive when exposures were extended to 1-3 h, and was more slowly reversible. These results suggest that Hg2+ can impair glial glutamate transport reversibly at exposure levels that do not compromise some other vital cell functions.
抑制谷氨酸转运是中枢神经系统中谷氨酸引起兴奋性毒性损伤的潜在间接原因。汞离子是金属汞蒸气据信发挥其神经毒性作用的形式，是一种已知的氨基酸转运抑制剂。本研究通过比较测量2-脱氧葡萄糖摄取来检测HgCl₂抑制小鼠脑星形胶质细胞中谷氨酸转运的特异性。2-脱氧葡萄糖摄取是葡萄糖利用的指标，反映了Na⁺，K⁺-ATP酶和己糖激酶的功能，并且对Na⁺进入敏感。这些星形胶质细胞培养物中谷氨酸转运的动力学参数、离子依赖性和底物特异性与常见的X-AG系统一致。急性暴露于0.5微摩尔HgCl₂可使谷氨酸转运的初始速率降低50%，但不影响2-脱氧葡萄糖摄取。谷氨酸转运未被Al³⁺、Pb²⁺、Co²⁺、Sr²⁺、Cd²⁺或Zn²⁺（10微摩尔氯化物形式）显著抑制。0.5微摩尔HgCl₂对谷氨酸转运的抑制作用可迅速逆转。当暴露延长至1-3小时时，1-2微摩尔HgCl₂的作用是渐进性的，且逆转更慢。这些结果表明，Hg²⁺在不损害某些其他重要细胞功能的暴露水平下可可逆地损害胶质细胞谷氨酸转运。
